This invention relates to the liquid storage of physiological material and, more particularly, to an improved storage procedure involving temperature cycling of the stored material to more effectively preserve its function and viability.
The liquid storage of human cells or tissue for subsequent use in transfusions, transplanatations or the like, has conveniently been carried out by maintaining such cells or tissue in suspension or immersion in physiological solution at normal refrigerator temperature, i.e., at about 4.degree. C. This is the procedure which most blood banks have typically employed for many years for storing red blood cell, white blood cell, and platelet concentrates in plasma. However, 4.degree. C. storage has certain limitations which substantially hinder its effectiveness for storage periods beyond about twenty-four hours.
A tremendous increase in recent years in the use of platelet transfusions for the control of thrombocytopenic bleeding, has led to a number of recent studies designed to improve the efficiency of platelet collection and storage techniques. The results of these studies have indicated that in certain respects, 22.degree. C. storage of platelets is preferably to 4.degree. storage, particularly when the storage period is to be greater than about twenty-four hours. The primary disadvantage of the 4.degree. C. storage technique is that after about twenty-four hours at this temperature, the in vivo survival time of the transfused platelets drops from the "normal" level of about seven to eight days to a level of only about two to three days. With the 22.degree. C. storage technique, on the other hand, the in vivo survival times of the transfused platelets are maintained at "normal" levels for up to seventy-two hours of storage time. However, this improved platelet viability provided by the 22.degree. C. storage technique in comparison with 4.degree. C. storage, is offset by a loss in the aggregating and hemostatic functions of the platelets upon their transfusion. Thus, while platelets stored at 4.degree. C. for up to seventy-two hours of storage retain their immediate hemostatic effectiveness upon transfusion, platelets stored at 22.degree. C. for the same period of time exhibit a significantly delayed hemostatic effectiveness upon transfusion. In addition to this loss in function, there is an increased risk of bacterial contamination for those platelets stored at 22.degree. C. Hence, particularly where the stored platelets are to be used primarily for achieving immediate hemostasis, rather than mere prophylaxis, 4.degree. C. storage offers important benefits which are not available with the 22.degree. C. storage technique. Moreover, neither of these storage techniques has been found to be very effective for storing platelets for storage periods longer than about seventy-two hours.
It has previously been demonstrated that the function and viability of human cells and tissue are significantly affected by the presence or absence in the cells or tissue of microtubules. Losses in function and viability are generally associated with losses in microtubules. In human platelets, microtubules are thought to be essential for maintenance or stabilization of cell shape, and are necessary for secretion. Loss of platelet microtubules has resulted in loss of spreading capabilities, inhibition of aggregation, and probably contributes to spontaneous aggregation seen in stirred suspensions of cold platelets. In other cells, microtubules are involved in a variety of important cellular functions, and the processes of microtubule disassembly and reassembly in these cells are known to reflect complex biochemical mechanisms.
It has also previously been demonstrated that microtubules are sensitive to cold temperatures, and that irreversible microtubule disassembly occurs in platelets maintained at 4.degree. C. continuously for more than about twenty-four hours. In view of the correlation between loss of microtubules in cells and tissue, and losses in their function and viability, it therefore appears likely that inhibiting irreversible microtubule disassembly is an important factor in developing a more efficient procedure for the storage of cells and tissue.